Perlecan is required for FGF-2 signaling in the neural stem cell niche

被引:65
作者
Kerever, Aurelien [1 ]
Mercier, Frederic [2 ]
Nonaka, Risa [1 ]
de Vega, Susana [1 ]
Oda, Yuka [1 ]
Zalc, Bernard [3 ,4 ,5 ]
Okada, Yohei [6 ,7 ]
Hattori, Nobutaka [8 ]
Yamada, Yoshihiko [9 ]
Arikawa-Hirasawa, Eri [1 ,8 ]
机构
[1] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo 1138421, Japan
[2] Univ Hawaii, John A Burns Sch Med, Dept Trop Med & Infect Dis, Honolulu, HI 96822 USA
[3] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere CRICM, UMRS 975, F-75013 Paris, France
[4] Univ Paris 06, INSERM, U975, F-75013 Paris, France
[5] CNRS, UMR 7225, F-75013 Paris, France
[6] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 160, Japan
[7] Keio Univ, Sch Med, Kanrinmaru Project, Tokyo, Japan
[8] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan
[9] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA
基金
美国国家卫生研究院;
关键词
FIBROBLAST-GROWTH-FACTOR; ADULT SUBVENTRICULAR ZONE; MAMMALIAN BRAIN; OLFACTORY-BULB; VASCULAR NICHE; CYCLIN D2; PROLIFERATION; NEUROGENESIS; BINDING; PROTEOGLYCAN;
D O I
10.1016/j.scr.2013.12.009
中图分类号
Q813 [细胞工程];
学科分类号
摘要
In the adult subventricular zone (neurogenic niche), neural stem cells double-positive for two markers of subsets of neural stem cells in the adult central nervous system, glial fibrillary acidic protein and CD133, lie in proximity to fractones and to blood vessel basement membranes, which contain the heparan sulfate proteoglycan perlecan. Here, we demonstrate that perlecan deficiency reduces the number of both GFAP/CD133-positive neural stem cells in the subventricular zone and new neurons integrating into the olfactory bulb. We also show that FGF-2 treatment induces the expression of cyclin D2 through the activation of the Akt and Erk1/2 pathways and promotes neurosphere formation in vitro. However, in the absence of perlecan, FGF-2 fails to promote neurosphere formation. These results suggest that perlecan is a component of the neurogenic niche that regulates FGF-2 signaling and acts by promoting neural stem cell self-renewal and neurogenesis. (C) 2013 The Authors. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:492 / 505
页数:14
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